POS1417 CATEGORIZATION OF PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS USING DISEASE ACTIVITY, PATIENT-REPORTED OUTCOMES AND TRANSCRIPTOMIC SIGNATURES
Authors: R. Arcani, E. Jouve, L. Chiche, N. Jourde-Chiche
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Patients with systemic lupus erythematosus (SLE) display symptoms that are not always related to disease activity and may distort clinical trial results. Recently, a clinical categorization based on the presence of type 1 (inflammatory manifestations) and/or type 2 (widespread pain, fatigue, depression) symptoms has been proposed in SLE (1) and tested in a cohort of 212 patients [2]. This allowed the categorization of patients at the time of clinical assessment into four distinct groups: "type 1": patients displaying only type 1 symptoms; "type 2": patients displaying only type 2 symptoms; "mixed": patients displaying both type 1 and type 2 symptoms; "minimal": patients with no symptoms. This classification was built upon the SLEDAI score (type 1 symptoms), which is widely available in SLE studies, and on American College of Rheumatology fibromyalgia criteria (type 2 symptoms), which are less commonly used in SLE and are rarely available. <h3>Objectives</h3> Our aim was to develop a type 2 score derived from the Short-Form health survey (SF-36) to categorize SLE patients and to compare immunological and transcriptomic profiles between groups. <h3>Methods</h3> Seventeen items from the SF-36 were selected to build a type 2 score for 50 SLE patients (100 visits; LUPUCE cohort) and the SLEDAI was used to define type 1 symptoms. Patients were categorized in four groups: minimal (no symptoms), type 1, type 2 and mixed (both type 1 and type 2 symptoms). Clinical, immunological and transcriptomic profiles (3) were compared between the groups. The PSY-LUP cohort (from a study evaluating the psycho-social consequences of SLE) (4) was an independent cohort used to confirm the results found in the LUPUCE cohort. <h3>Results</h3> Type 2 scores ranged from 0 to 31, with a cut-off value of 14 (75th percentile) that was the chosen threshold to define the type 2 symptoms. The sample categorization was: minimal in 39%, type 1 in 37%, type 2 in 9% and mixed in 15%. The type 2 score was calculated in an independent cohort of 100 SLE patients (PSY-LUP cohort). This showed a similar pattern of values to the LUPUCE cohort: the score ranged from 0 to 33, and 23% of patients were above the threshold of 14. Type 2 patients were older than minimal patients (52 vs. 31 years, p=0.016) and had a longer disease duration than type 1 and mixed patients (10 vs. 5 years and 10 vs. 2 years, p=0.011, respectively). Immunological data (elevated anti-dsDNA antibodies, anti-dsDNA level, low C3 and/or C4) and modular interferon (IFN) signatures (modular IFN score, number of activated IFN modules and level of regulation of each IFN module) did not differ between the groups. <h3>Conclusion</h3> Patients with SLE can be categorized into four clinical groups using the SLEDAI score and our SF-36-derived type 2 score. This categorization is non-redundant with immunological or transcriptomic profiles and could prove useful to stratify patients in clinical trials. <h3>References</h3> [1]Pisetsky DS, Clowse MEB, Criscione-Schreiber LG, Rogers JL. A novel system to categorize the symptoms of systemic lupus erythematosus. Arthritis Care Res (Hoboken) 2019;71:735–41. [2]Rogers JL, Eudy AM, Pisetsky D, Criscione-Schreiber LG, Sun K, Doss J, et al. Using clinical characteristics and patient-reported outcome measures to categorize systemic lupus erythematosus subtypes. Arthritis Care Res (Hoboken) 2021;73:386–93. [3]Chiche L, Jourde-Chiche N, Whalen E, Presnell S, Gersuk V, Dang K, et al. Modular transcriptional repertoire analyses of adults with systemic lupus erythematosus reveal distinct type I and type II interferon signatures. Arthritis Rheumatol 2014;66:1583–95 [4]NCT03913754 <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.